{"entity": "researcher", "timestamp": "2026-09-30T03:00:42.556Z", "family": "van Hall", "given": "Thorbald", "initials": "T", "orcid": "0000-0002-9115-558X", "affiliations": ["Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; adnane.achour@ki.se T.van_Hall@lumc.nl."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/abf6a9db2eda480daa8d0d306f2bf3bb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/abf6a9db2eda480daa8d0d306f2bf3bb"}}, "publications": [{"entity": "publication", "iuid": "fd073f0867574539b41124c5ae0ebb10", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fd073f0867574539b41124c5ae0ebb10.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fd073f0867574539b41124c5ae0ebb10"}}, "title": "The Immunogenicity of a Proline-Substituted Altered Peptide Ligand toward the Cancer-Associated TEIPP Neoepitope Trh4 Is Unrelated to Complex Stability.", "authors": [{"family": "Hafstrand", "given": "Ida", "initials": "I", "orcid": "0000-0002-1012-9532", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30b0065eee584566a6d75a1df61c0836.json"}}, {"family": "Doorduijn", "given": "Elien M", "initials": "EM"}, {"family": "Sun", "given": "Renhua", "initials": "R", "orcid": "0000-0002-8203-4946", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29b44e08db3a4482a6a40bbda52fe815.json"}}, {"family": "Talyzina", "given": "Anna", "initials": "A", "orcid": "0000-0001-9727-7441", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f46df1e45fb0485e9b2ef6fe263e4016.json"}}, {"family": "Sluijter", "given": "Marjolein", "initials": "M"}, {"family": "Pellegrino", "given": "Sara", "initials": "S", "orcid": "0000-0002-2325-3583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c0d6ed24c4914ce4b6cd0f699f121b52.json"}}, {"family": "Sandalova", "given": "Tatyana", "initials": "T", "orcid": "0000-0002-7694-6420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ea3d2ec9e94fe3876f88bd0786c24b.json"}}, {"family": "Duru", "given": "Adil Doganay", "initials": "AD"}, {"family": "van Hall", "given": "Thorbald", "initials": "T", "orcid": "0000-0002-9115-558X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abf6a9db2eda480daa8d0d306f2bf3bb.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A", "orcid": "0000-0003-0432-710X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65fba324156a4fcbafbe636e642587a9.json"}}], "type": "journal article", "published": "2018-04-15", "journal": {"title": "J. Immunol.", "issn": "1550-6606", "volume": "200", "issue": "8", "pages": "2860-2868", "issn-l": "0022-1767"}, "abstract": "Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP. In this study, we demonstrate that substitution of the nonanchoring position 3 into a proline residue of the first identified TEIPP peptide, the murine Trh4, results in significantly enhanced recognition by antitumor CTLs toward the wild-type epitope. Although higher immunogenicity has in most cases been associated with increased MHC/peptide complex stability, our results demonstrate that the overall stability of H-2Db in complex with the highly immunogenic altered peptide ligand Trh4-p3P is significantly reduced compared with wild-type H-2Db/Trh4. Comparison of the crystal structures of the H-2Db/Trh4-p3P and H-2Db/Trh4 complexes revealed that the conformation of the nonconventional methionine anchor residue p5M is altered, deleting its capacity to form adequate sulfur-\u03c0 interactions with H-2Db residues, thus reducing the overall longevity of the complex. Collectively, our results indicate that vaccination with Thr4-p3P significantly enhances T cell recognition of targets presenting the wild-type TEIPP epitope and that higher immunogenicity is not necessarily directly related to MHC/peptide complex stability, opening for the possibility to design novel peptide vaccines with reduced MHC/peptide complex stability.", "doi": "10.4049/jimmunol.1700228", "pmid": "29507106", "labels": [], "xrefs": [{"db": "pii", "key": "jimmunol.1700228"}], "notes": [], "created": "2018-12-05T12:43:40.608Z", "modified": "2026-09-23T13:02:47.525Z"}]}